18 months of FDA’s Core Patient-Reported Outcomes in Cancer Clinical Trials Guidance – have we seen its impact?
Florence Mowlem, PhD, Chief Scientific Officer
Oncology continues to be one of the fastest growing and most heavily funded therapeutic areas globally. Approximately 5,583 oncology studies were initiated or ongoing globally between Jan 2025 to date1, with~18% increase in oncology study starts projected until 2030.
Historically, oncology trial endpoints have focused primarily on objective clinical outcomes, such as overall survival or time to disease progression. However, the oncology landscape is evolving alongside advances in available treatments, and therapies with similar efficacy based on traditional clinical endpoints may differ significantly in outcomes that matter most to patients.
“It turns out that what is really bothering the patient and what is really bothering the doctor can be radically different things…. patients are true experts in their disease.”
Dr. Janet Woodcock, Director – Center for Drug Evaluation and Research2
As a result, there is increasing recognition of the importance of understanding the trade-off between quality of life (QoL) and length of life. QoL is a complex and multifaceted concept that can vary greatly between individuals, encompassing physical, emotional, social, and functional well-being. Research in oncology populations has demonstrated that patients value not only life extension, but also how treatment impacts their daily QoL and the well-being of their families. These insights highlight the growing importance of incorporating patient-reported outcome measures (PROMs) into oncology research and treatment evaluation3.
The Regulatory Perspective
FDA4 and EMA5 encourage the use of PROs in cancer clinical trials to:
- Provide a patient-focused assessment of the burden and impact of disease
- Add information on the clinical benefit of a therapy by complementing efficacy and safety data with patient-reported evaluation
- Attempt to differentiate two treatments in the non-inferiority trial setting, where the primary endpoint is an objective measure
- Provide information to facilitate more accurate future patient-physician communication in terms of quality of the survival time remaining and burden of treatment-related morbidities.
Building upon these efforts, in late 2024, the FDA released guidance on capture of PROs in Oncology trials, outlining recommendations for a core set of PROs in cancer clinical trials6. One of the aims of this guidance is to encourage standardization regarding the core domains that are measured in oncology studies, which would enable more comparison across trials based on commonality in measurement domains across trials, and maximize the regulatory utility of submitted PRO information. Table 1 outlines the five core domains. The FDA Guidance also includes considerations for the frequency of PRO assessment.
Within the FDA Guidance, considerations for reducing missing data proactively are outlined, including a completion monitoring strategy, such as reminders to patients and methods to lessen burden, such as electronic PRO capture, which can also facilitate data collection outside of the clinic environment. Only measuring outcomes at site visits that occur at the beginning of a treatment-cycle can be misleading; for example, in relation to side effects, this assessment time-point is likely to occur after recovery from the previous cycle and before the expected time of greatest toxicity of the next cycle, and therefore not provide an accurate reflection of the patient perspective.
Additional literature in the field also shows preference for electronic data capture in this population to increase compliance7.
Table1. Core PRO domains to measure in cancer clinical trials, as outlined by the FDA
| Core Domain | Description |
| Disease-related Symptoms | This will be specific to the cancer-type, where a group of common cardinal symptoms exists. |
| Symptomatic Adverse Events | The NCI PRO-CTCAE is an item library of 78 symptomatic toxicities, that offers a standardized and flexible approach to measuring symptomatic adverse events from the patient perspective, though selection of a concise set of the most important symptomatic AEs expected to occur. |
| Overall side effect impact summary measure | As different patients place different emphasis on certain side effects, a global summary measure is helpful. |
| Physical Function | This concept has been shown to be important to patients and can also offer prognostic value. |
| Role Function (QoL) | The ability to work and carry out daily activities is important to patients. |
Has this Translated Into Actual Change in PROM Inclusion in Clinical Trials?
A publication in Value in Health8, titled “A Review of Patient-Reported Outcomes Labeling for Oncology Drugs Approved by the FDA and the EMA (2012-2016)”, found 49 drugs with 64 unique oncology indications (45 with PRO data) were approved by both the FDA and the EMA, with none (0%) receiving PRO labeling from the FDA. 21 indications (32.8%) had PRO-related language in the summary of product characteristics from the EMA. Both the EMA and FDA cited missing data as problematic for the interpretation of efficacy.
Another publication titled “A review of patient-reported outcomes used for regulatory approval of oncology medicinal products in the European Union between 2017 and 2020” found that across a total of 128 oncology indications, which corresponded to 76 medicines that were approved, 78.1% included PROMs in the confirmatory trials. Across all the confirmatory trials, 57.7% included the PROMs as a secondary endpoint9.
Of ~1044 studies set to start from now until the end of 2030, across all trial phases, approximately 13% listed on Globaldata.com made reference to QoL measures, of which around half were Phase 2 or 3. Similar results were found on Clinicaltrials.gov for QoL and PROMs.
This would suggest that despite momentum on the inclusion of PROMs in oncology trials, progress on their inclusion remains slow and not yet widely adopted.
Concluding Remarks
It is positive to see the regulatory emphasis being placed on the inclusion of PROMs in oncology clinical trials, and indeed it is beneficial in all therapeutic areas. Further utilization comes from recommendations of core-domains to be measured from the patient perspective to drive consistency across drug development programs. There can be a misconception that this is only applicable to later phase trials where the data will be used for labeling claims; however, early phase trials offer the perfect opportunity to ensure the right items and measures are included in later stage trials, and that what is meaningful to patients is understood fully for inclusion in pivotal trials.
As always, we still have progress to make to ensure a well-rounded picture of new treatments from the patient perspective is captured and takes a more prominent role in drug development.
References:
[1] Globaldata.com
[2] PDUFA V Clinical Outcome Assessments Public Workshop, April 1,2015.
[4] Core Patient-Reported Outcomes in Cancer Clinical Trials Guidance for Industry, October 2024.